2-aminothiazole phosphates and phosphonates

ABSTRACT

COMPOUNDS OF THE FORMULA   2-(R3-P(=S)(-R4)-S-CH2-CO-N(-R2)-),4-R,5-R1-THIAZOLE   IN WHICH R IS HYDROGEN; ALKYL; NAPHTHYL; PHENYL; MONO OR DI SUBSTITUTED PHENYL WHEREIN THE SUBSTITUENTS ARE HALOGEN, NITRO, ALKYL; OR THE GROUP-CH2-S-R5 IN WHICH R5 IS ALKYL, PHENYL, BENZYL, OR HALOPHENYL; R1 IS HYDROGEN; ALKYL; PHENYL; MONO RO DI SUBSTITUTED PHENYL WHEREIN THE SUBSTITUENTS ARE HALOGEN, NITRO, ALKYL; NITRO; OR HALOGEN; R2 IS HYDROGEN, ALKYL; ALLYL OR PHENYL; R3 IS ALKOZY, AND R4 IS ALKOZY OR ALKYL, AND AS INSECTICIDES AND ACARICIDES.

United States Patent Office 3,591,600 Patented July 6, 1971 ABSTRACT OF THE DISCLOSURE Compounds of the formula l I i I l/ R Jar-dormer in which R is hydrogen; alkyl; naphthyl; phenyl; mono or di substituted phenyl wherein the substituents are halogen, nitro, alkyl; or the group -CH 'SR in which R is alkyl, phenyl, benzyl, or halophenyl;

R is hydrogen; alkyl; phenyl; mono or di substituted phenyl wherein the substituents are halogen, nitro, alkyl; 2

nitro; or halogen;

R is hydrogen, alkyl; allyl or phenyl;

R is alkoxy, and

R is alkoxy or alkyl and the use of these compounds as insecticides and acaricides.

in which R is hydrogen; alkyl having 1 to 5 carbon atoms,

preferably methyl; naphthyl; phenyl, mono or di sub- 4 stituted phenyl wherein the substituents are halogen, preferably chlorine, nitro, alkyl having 1 to 5 carbon atoms, preferably methyl or the group --CH -SR in which R is alkyl having 1 to 5 carbon atoms, preferably 1 to 2 carbon atoms, phenyl, benzyl, or halophenyl, preferably 5 chlorphenyl;

R is hydrogen, alkyl having 1 to 5 carbon atoms, preferably methyl, phenyl, mono or di substituted phenyl wherein the substituents are halogen, preferably chlorine, nitro, alkyl having 1 to 5 carbon atoms, preferably methyl; nitro; or halogen, preferably chlorine;

R is hydrogen, alkyl having 1 to 4 carbon atoms, preferably methyl; allyl or phenyl;

R is alkoxy having 1 to 5 carbon atoms, and

R is alkoxy having 1 to 5 carbon atoms, preferably 1 to 3 carbon atoms, or alkyl having 1 to 5 carbon atoms, preferably 1 to 2 carbon atoms.

The term halogen as used herein includes chlorine, bromine, iodine, and fluorine. The term halo as used herein includes chloro, bromo, iodo, and fluoro.

The compounds having the formula in which R, R, R and R are as defined above by the following reactions:

The reaction of a haloacetamide with a salt of an organic phosphate to form an acetamido phosphate is wellknown:

The same general method is used in the preparation of the compounds of this invention; however, certain modifications of the above reaction have been made to simplify the procedure and to insure in most instances, high yields. The modifications include the use of anhydrous triethylamine which obviates the isolation of phosphate salt, and dimethyl formamide as a solvent medium which facilitates and promotes the reaction.

Although other solvents such as ketones, alcohols, benzone-H O mixtures, etc., can be used, DMF has been found most advantageous with regard to reaction times and yields. It has also been found that a small excess of triethylamine is advantageous in bringing the reaction to completion.

After completion of the reaction between the chloroacetamide and the phosphate, or phosphonate amine salt, the product is conveniently isolated by pouring the mixture into water. If the product is a solid, it is filtered off and recrystallized if desired. If the product is a liquid, it can be extracted with a solvent such as benzene, chloroform, etc.

Chloroacetamide derivatives are used for economic reasons; however, bromo or iodoacetamides can also be used.

Preparation of the compounds of this invention is illustrated by the following examples.

EXAMPLE I 2,0,0-diethylphosphorodithioylacetamidothiazole N I H i I S/NHCCH2 (0 2 92 18.6 gm. (0.1 M) of diethyl dithiophosphoric acid is diluted with 10 ml. of dimethyl formamide. The mixture is cooled in an ice-bath and made slightly basic (below 30 C.) with anhydrous triethylamine (about 13.8 cc.; 0.1 M, is used). This solution is then added to 12.3 gm. (0.07 M) of 2-chloroacetamidothiazole dissolved in 50 ml. of dimethylformamide. A moderate temperature rise occurs on mixing. The reaction is completed by stirring at 50-60 C. for one hour. The reaction mixture is poured into 200 ml. of ice-water and the solid, which separated, is filtered off, washed with cold water, and air-dried to give the desired product, 21.4 gm. (94% of theory), M.P. 12l124 C.

3 4 A nalysis.Theory (percent): C, 33.1; H, 4.61; N, 8.59; that are preparable according to the procedure described P, 9.51; S, 29.5. Found (percent): C, 32.55; H, 4.56; N, hereto. Compound numbers are assigned to each com- 8.35; P, 9.61; S, 28.85. pound and are used throughout the remainder of the ap- The following is a table of certain selected compounds plication.

TABLE I l 1 52 IU\ N-CCHzSP Compound up or Number R R1 R2 R4 R3 M P (C 1 H H H 021150 021-150 121-124 2 H H H (EH30 (EH30 113-115" 3 H H H CzHs i-CaH7O 93)5 4 CH3 H H CZHSO 21-150 1 5598 5 CH3 H H 1-C1H10 1-C5H70 1 5560 6 CH3 :H 11 11-031170 Il-C3H7O 1 5428 7. CH3 H II CzHs i-C3H7O 1 5682 s CH; 11 H CHaO (EH 1 5688 H H C1150 CHZO 1. 6153 H H C2115 i-C1H1O 1.6158 II H l1-C3H7O l1-C3H7O 1. 6090 H H C2115 021150 03-95" H II Same 021-1 0 116-123" 15 H H 10 Same -74 10 c1- H H d0 1. 0228 H H (EH30 CHaO 117420 II H C 2H5O 021150 CH3 H Same Same 1. 5600 CH3 H 02115 1031170 1. 5646 CH; II Same i-C4H9O 1. 5523 H 021150 C21I5o 114-119 24 CH3 H Same C2H5O 132-135 25 H H H i-CuiIIqO 1.5866

26 0113 II C1130 C1130 1.5831

27 H H H C1115 Same -93 28 H 11 Same 10.1150 1. 5000 11 r10 i-OiHvO 1. 5500 H ..d0 CHaO 1.5775

H C2H5O C 21150 1. 6080 II Same 011150 -108" 34 Same as above 11 H CQIIB l-C5H1O 1. 597B 35 (321158 0112 H II CzHaO CzH5O 0 36 Same as above H H C2H5 Same 1. 5963 37 Cl- H H 02m d0 1. 5920 38 H N0 H CzH ..(]0. 83-86 39 H Br H Same ..do 7780 TABLE ICntinued Compound Number R R1 R2 N02 H Br H H H Br H H CH2 H CH H CH3 H H 0 11 0 C2H5O 1. 5043 H CH2CH=CH 0 11 Same 1. 5681 H Same as above C2H5 ...do 1. 5620 H ......d0 C2115 P031170 1. 5620 H Same 14341190 1.5590

H ..do 0213.0 1. 5953 11 021150 Same 1. 5070 H C2115 i-o3H10 1. 5701 H Same 1-O4H9O 1. 5685 H 2 d() 2115 1. 5800 H Same as above" 021E1 0 Same 1. 5640 H H C2115 1-04Hg0 1. 5755 H H Same l-C H O 65-68 61 Same as above H H .-...d0 OH3O 142-146 62 @OEHSOH: H H --.do... 0211.0 1. 5988 01 e3 CH1 H 021150 Same 109-111 Same as above H C2115 do 116-119 H Same i-C3H7O H d0. i-C4H9O 1.5980 H do (EH 0 13s-141 H H 0 21 0 o H o 169-174" H 1.6328 H 1. 6240 H 1.6195 H 140-144 H C2H5O CzI-IsO 1. 6070 Same as above. H CZHE 1. 6165 .1. H3SCH2 H 02115 1.5900 Same as above H H 021115 1. 5940 Waxy solid.

INSECTICIDAL EVALUATION TESTS to five days old were introduced into the cake and the The following insect species were used in evaluation percent mortahty was r.ecorded after 48 hours The tests for insecticidal activity 50 values are expressed in terms of g. per 25 female flies. The results of this insecticidal evaluation test are given (1) Housefly (HF)-Musca domestlca (Linn) in m 1 under Lyglls g y {1651167118 In the lygus bug (LB) Lygus hesperus test, ten to twenty- Bean Aphld P fabae p) five two-week old nymphs of lygus bug were placed in The housefly (HF) was mad in evaluation tests f separate circular cardboard cages sealed on one end with lected compounds as insecticides by the following proce- P and 6d by a cloth netting on the other. dure. A stock Solution containing 100 [Lg/m1 of the Aliquots of the toxicants, dissolved in an appropriate soltoxicant in an appropriate solvent was prepared. Aliquots f were muted Water Contammg of a of this solution were combined with 1 milliliter of an tmg agent 221 Polyoxyether of al-kylated acetone-peanut oil solution in a glass petri dish and al- PhePols blended Wlth organ: sulfonates)- Test f' lowed to dry The aliquots were there to achieve desired trations ranged from 0.05% downward to that at which toxicant concentration ranging from 100 ,ttg./per petri dish to that at which 50% mortality was attained. The petri dishes were placed in a circular cardboard cage, closed on the bottom with cellophane and covered on top with cloth netting. Twenty-five female houseflies, three 50% mortality was obtained. Each of the aqueous suspensions of the candidate compounds were sprayed onto the insect through the cloth netting by means of a handspray gun. Percent mortality in each case recorded after 24 and 72 hours counts were made to determine living and dead insects. The LD-SO values expressed as percent of toxicant in the aqueous spray were calculated and recorded. These values are reported under the column LB in Table II.

The insect species black bean aphid (BA) Aphis fabae (Scop.) was also employed in the test for insecticidal activity. Young nasturtium (Tropaeolum sp.) plants, approximately 2 to 3 inches tall, were used as the host plants for the bean aphid. The host plant was infested with approximately 50-75 of the aphids. The test chemical was dissolved in acetone, added to water which contained a small amount of Sponto 221, an emulsifying agent. The solution was applied as a spray to the infested plants. Concentrations ranged from 0.05 percent downward until an LD-50 value was achieved. These results are given in Table II under the Column BA.

ACARICIDAL EVALUATION TEST The two-spotted mite (2SM), Tetranychus urticae (Koch), was employed in tests for m iticides. Young pinto bean plants or lima bean plants (Phaseolus sp.) in the primary leaf stage were used as the host plants. The young pinto bean plants were infested with about 100 mites of various ages. Dispersions of candidate materials were prepared by dissolving 0.1 gram in 10 ml. of a suitable solvent, usually acetone. Aliquots of the toxicant solutions were suspended in water containing 0.002% v./v. Sponto 22l, polyoxyethylene ether sorbitan monolaurate, an emulsifying agent, the amount of water being sufiicient to give concentrations of active ingredient ranging from 0.05% to that at which 50% mortality was obtained. The test suspensions were then sprayed on the infested plants to the point of run off. After 7 days, mortalities of the post-embryonic form was determined. The percentage of kill was determined by comparison with control plants which had not been sprayed with candidate compounds. The LD-50 value was calculated using well-known procedures. These values are reported under the columns ZSM-PE and ZSM-Eggs, in Table II.

SYSTEMIC EVALUATION TEST This test evaluates the root absorption and upward translocation of the candidate systemic compound. The beam aphid (BA) Aphis fabae (Scop.) was employed in the test for systemic activity.

Young nasturtium plants were used as the host plants for the bean aphid. The host plants were transplated into one pound of soil that had been treated with the candidate compound. Immediately after planting in the treated soil, the plants were infested with the aphids. Concentrations of toxicant in the soil ranged from 10 ppm. per pound of soil downward until an LD-50 value was obtained. Mortality was recorded after 72 hours.

The percentage of kill of the test species was determined by comparison with control plants placed in distilled water or untreated soil. The LD-SO values were calculated. These systemic test results are reported in Table II under the column Ba-Sys.

TABLE II.(LD VALUES) Thiazole Phosphates Percent 2SM, percent Compound HF, BA-Sys., Number pg. LB BA p.p.1n. PE Eggs Percent 28M, percent Compound HF, A-Sys., Number 114;. LB BA p.p.m PE Eggs As those in the art are well aware, various techniques are available for incorporating the active component or toxicant in suitable pesticidal compositions. Thus, the pesticidal compositions can be conveniently prepared in the form of liquids or solids, the latter preferably as homogeneous free-flowing dusts commonly formulated by admixing the active component with finely divided solids or carriers as exemplified by talc, natural clays, diatomaceous earth, various flours such as walnut shell, wheat, soya bean, cottonseed and so forth.

Liquid compositions are also useful and normally comprise a dispersion of the toxicant in a liquid media although it may be convenient to dissolve the toxicant directly in a solvent such as kerosene, fuel oil, xylene, alkylated naphthalenes or the like and use such organic solutions directly. However, the more common procedures is to employ dispersions of the toxicant in an aqueous medium and such compositions may be produced by forming a concentrated solution of the toxicant in a suitable organic solvent followed by dispersion in water, usually with the aid of surface active agents. The latter, which may be anionic, cationic or nonionic types, are exemplified by sodium stearate, potassium oleate and other alkaline metal soaps and detergents such as sodium lauryl sulfate, sodium naphthalene sulfonate, sodium alkyl naphthalene sulfonate, methyl cellulose, fatty alcohol ethers, polyglycol fatty acid esters, and other polyoxyethylene surface active agents. The proportion of these agents commonly comprises 115% by weight of the pesticidal compositions although the proportion is not critical and may be varied to suit any particular situation.

9 I claim: 1. A compound of the formula:

R4 in which R is hydrogen, alkyl having 1 to .5 carbon atoms; naphthyl; phenyl, mono or di substituted phenyl, wherein the substituents are halogen, nitro, alkyl having 1 to 5 carbon atoms; or the group CH SR in which R is alkyl having 1 to 5 carbon atoms, phenyl, benzyl, or halophenyl;

R is hydrogen, alkyl having 1 to 5 carbon atoms, phenyl, mono or di substituted phenyl wherein the substituents are halogen, nitro, alkyl having 1 to 5 carbon atoms, nitro; or halogen;

R is hydrogen, alkyl having 1 to 4 carbon atoms; allyl or phenyl;

R is alkoxy having 1 to 5 carbon atoms, and

R is alkoxy having 1 to 5 carbon atoms, or alkyl having 1 to 5 carbon atoms.

2. The compound of claim 1 in which R is phenyl, R

is hydrogen, R is hydrogen, R is alkoxy, having 1 to 5 carbon atoms, and R is alkyl having 1 to 5 carbon atoms.

3. The compound of claim 1 in which R is hydrogen, R is hydrogen, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, and R is alkyl having 1 to 5 carbon atoms.

4. The compound of claim 1 in which R is methyl, R is hydrogen, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, and R is alkyl having 1 to 5 carbon atoms.

5. The compound of claim 1 in which R is methyl, R

is hydrogen, R is methyl, R is alkoxy, having 1 to 5 carbon atoms, and R is alkyl having 1 to 5 carbon atoms.

6. The compound of claim 1 in which R is nitrophenyl, R is methyl, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, and R is alkyl having 1 to 5 carbon atoms.

7. The compound of claim 1 in which R is hydrogen, R is hydrogen, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, and R is alkoxy having 1 to 5 carbon atoms.

8. The compound of claim 3 in which R is isopropoxy, and R is ethyl.

9. The compound of claim 3 in which R is ethoxy, and R is ethyl.

10. The compound of claim 3 in which R is isobutoxy and R is ethyl.

11. The compound of claim 4 in which R is isopropoxy and R is ethyl.

12. The compound of claim 6 in which R is isopropoxy, and R is ethyl.

References Cited UNITED STATES PATENTS 3,055,910 9/1962 Dickson et al. 260-306.8R 3,406,179 10/ 1968 Jamison 424-200 3,517,027 6/ 1970 Largman 424-200 ALEX MAZEL, Primar Examiner R. J. GALLAGHER, Assistant Examiner US. Cl. X.R. 424-200 

